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Investigation of the genetic toxicity by dextran-coated superparamagnetic iron oxide nanoparticles (SPION) in HepG2 cells using the comet assay and cytokinesis-block micronucleus assay

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Abstract

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPION) have been commercially used for medical applications, such as magnetic imaging or targeted drug delivery, etc. Despite of this usefulness, there are continuous controversies on safety/toxicity of various SPIONs. In the case of dextran-SPION, the reported adverse effects include the cytotoxicity, oxidative stress and DNA damage in many cell types. In this study, the genetic toxicity of dextran-SPION in human hepatoma (HepG2) cells was evaluated with comet assay and cytokinesis-block micronucleus (CBMN) assay. Dextran-SPION did not inhibit cell proliferation as a function of dose and time. The comet assay indicated that 5 μg/mL of dextran-SPION induced a significant DNA strand breaks. A dose-dependent increase of the micronucleus (MN) frequency was observed in CBMN assay. The formation of intracellular reactive oxygen species (ROS) in HepG2 cells was induced by dextran-SPION. The results demonstrated that dextran-SPION exerted genetic toxicity in HepG2 cells. Also, it suggests that a mechanism by which dextran-SPION triggers the DNA and chromosomal damage in HepG2 cells may be via the generation of intracellular ROS.

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References

  1. Ito, A., Shinkai, M., Honda, H. & Kobayashi, T. Medical application of functionalized magnetic nanoparticles. J. Biosci. Bioeng. 100, 1–11 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Huber, D. L. Synthesis, properties, and applications of iron nanoparticles. Small 1, 482–501 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Mahmoudi, M., Simchi, A., Milani, A. S. & Stroeve, P. Cell toxicity of superparamagnetic iron oxide nanoparticles. J. Colloid Interface Sci. 336, 510–558 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Duguet, E., Vasseur, S., Mornet, S. & Devoisselle, J. M. Magnetic nanoparticles and their applications in medicine. Nanomedicine (Lond) 1, 157–168 (2006).

    Article  CAS  Google Scholar 

  5. Gupta, A. K. & Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Mahmoudi, M., Hofmann, H., Rothen-Rutishauser, B. & Petri-Fink, A. Assessing the in vitro and in vivo toxicity of superparamagnetic iron oxide nanoparticles. Chem. Rev. 112, 2323–2338 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Ayala, A., Muoz, M. F. & Arguelles, S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med. Cell. Longev. 2014, 360438 (2014).

    Article  Google Scholar 

  8. Srinivasan, A., Lehmler, H. J., Robertson, L. W. & Ludewig, G. Production of DNA strand breaks in vitro and reactive oxygen species in vitro and in HL-60 cells by PCB metabolites. Toxicol. Sci. 60, 92–102 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Wu, H. et al. Reactive oxygen species-related activities of nano-iron metal and nano-iron oxides. J. Food Drug Anal. 22, 86–94 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Bulte, J. W. et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat. Biotechnol. 19, 1141–1147 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Veranth, J. M. et al. Cytokine responses of human lung cells (BEAS-2B) treated with micron-sized and nanoparticles of metal oxides compared to soil dusts. Part Fibre. Toxicol. 4, 2 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hafeli, U. O. et al. Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery. Mol. Pharm. 6, 1417–1428 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Ankamwar, B. et al. Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells. Nanotechnology 21, 75102 (2010).

    Article  CAS  PubMed  Google Scholar 

  14. Singh, N. Conference scene -nanotoxicology: health and environmental impacts. Nanomedicine (Lond) 4, 385–390 (2009).

    Article  Google Scholar 

  15. Toyokuni, S. Iron-induced carcinogenesis: the role of redox regulation. Free Radic. Biol. Med. 20, 553–566 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Toyokuni, S. Iron and carcinogenesis: from Fenton reaction to target genes. Redox Rep. 7, 189–197 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Yu, M., Huang, S., Yu, K. J. & Clyne, A. M. Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture. Int. J. Mol. Sci. 13, 5554–5570 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jha, R. K. et al. An emerging interface between life science and nanotechnology: present status and prospects of reproductive healthcare aided by nano-biotechnology. Nano Rev. 5, 10.3402/nano.v5.22762 (2014).

    Article  PubMed Central  Google Scholar 

  19. Uthaman, S. et al. Polysaccharide-coated magnetic nanoparticles for imaging and gene therapy. BioMed. Res. Int. 2015, 959175 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Karlsson, H. L., Cronholm, P., Gustafsson, J. & Möller, L. Copper oxide nanoparticles are highly toxic: A comparison between metal oxide nanoparticles and carbon nanotubes. Chem. Res. Toxicol. 21, 1726–1732 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Mojica Pisciotti, M. L. et al. In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting. J. Biomed. Mater. Res. B Appl. Biomater. 102, 860–868 (2014).

    Article  CAS  PubMed  Google Scholar 

  22. Singh, N., Jenkins, G. J. S., Asadi, R. & Doak, S. H. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev. 1, 10.3402/nano. v1i0.5358 (2010).

    Google Scholar 

  23. Scolastici, C. et al. Antigenotoxicity and antimutagenicity of lycopene in HepG2 cell line evaluated by the comet assay and micronucleus test. Toxicol. in Vitro 22, 510–514 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Maluf, S. W. Monitoring DNA damage following radiation exposure using cytokinesis-block micronucleus method and alkaline single-cell gel electrophoresis. Clin. Chim. Acta 347, 15–24 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Valdiglesias, V. et al. Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity. Environ. Mol. Mutagen. 56, 125–148 (2015).

    Article  CAS  PubMed  Google Scholar 

  26. Remya, N. S., Syama, S., Sabareeswaran, A. & Mohanan, P. V. Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications. Int. J. Pharm. 511, 586–598 (2016).

    Article  CAS  PubMed  Google Scholar 

  27. Könczöl, M. et al. Cytotoxicity and genotoxicity of sizefractionated iron oxide (magnetite) in A549 human lung epithelial cells: role of ROS, JNK, and NF-jB. Chem. Res. Toxicol. 24, 1460–1475 (2011).

    Article  PubMed  Google Scholar 

  28. Hong, S. C. et al. Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups. Int. J. Nanomedicine 6, 3219–3231 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Magdolenova, Z. et al. Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. Nanotoxicology 9(Suppl 1), 44–56 (2015).

    Article  CAS  PubMed  Google Scholar 

  30. Ma, P. et al. Intraperitoneal injection of magnetic Fe3O4-nanoparticle induces hepatic and renal tissue injury via oxidative stress in mice. Int. J. Nanomedicine 7, 4809–4818 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Mesárošová, M. et al. The role of reactive oxygen species in the genotoxicity of surfacemodified magnetite nanoparticles. Toxicol. Lett. 226, 303–313 (2014).

    Article  PubMed  Google Scholar 

  32. Kim, S. H. et al. Safety evaluation of zinc oxide nanoparticles in terms of acute dermal toxicity, dermal irritation and corrosion, and skin sensitization. Mol. Cell. Toxicol. 12, 93–99 (2016).

    Article  CAS  Google Scholar 

  33. Ying, E. & Hwang, H.-M. In vitro evaluation of the cytotoxicity of iron oxide nanoparticles with different coatings and different sizes in A3 human T lymphocytes. Sci. Total Environ. 408, 4475–4481 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Yang, L. et al. Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice. Nanoscale 7, 625–636 (2015).

    Article  CAS  PubMed  Google Scholar 

  35. Natarajan, A. T. & Darroudi, F. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens. Mutagenesis 6, 399–403 (1991).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Youn-Jung Kim.

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Seo, D.Y., Jin, M., Ryu, JC. et al. Investigation of the genetic toxicity by dextran-coated superparamagnetic iron oxide nanoparticles (SPION) in HepG2 cells using the comet assay and cytokinesis-block micronucleus assay. Toxicol. Environ. Health Sci. 9, 23–29 (2017). https://doi.org/10.1007/s13530-017-0299-z

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